title: Fludarabine and pharmacokinetic-targeted busulfan before allografting for adults with acute lymphoid leukemia.
abstract: We aimed to evaluate the safety and efficacy of fludarabine (FLU) and pharmacokinetic-targeted busulfan (BU) as conditioning regimen for hematopoietic cell transplantation (HCT) in adult patients with acute lymphoid leukemia (ALL). Forty-four patients with ALL (27 in first complete remission [CR1] and 17 in more advanced disease stage: 4 with primary induction failure [PIF], 12 in CR2, and 1 in CR3) received FLU and pharmacokinetic-targeted BU as preparative therapy for HCT. Grafts were T-replete, filgrastim-mobilized peripheral blood stem cells (PBSC). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus (TAC) and short-course methotrexate in 36 patients, TAC and sirolimus in 3, and TAC and mycophenolate mofetil in 5. Primary engraftment was achieved in all 44 patients. The cumulative incidence of transplant-related mortality (TRM) was 2% (95% confidence interval [CI] 0%-16%) at 100 days and 18% (95% CI 10%-34%) at 2 years. The 2-year cumulative incidence of relapse was 19% (95% CI 8%-41%) for those transplanted in CR1, and 48% (29%-80%) for those with more advanced disease. After a median follow-up of 32 months (range: 15-69 months), the 2-year overall survival (OS) was 54% (95% CI 39%-69%). Relapse-free survival (RFS) at 2 years was 63% (95% CI 45%-81%) for patients transplanted in CR1 and 34% (95% CI 11%-57%) for patients transplanted in more advanced disease. When compared to irradiation-containing regimens, FLU and PK-targeted BU appear safer and similarly effective in controlling ALL, providing a treatment option for adult patients with ALL.
authors.affiliation: Department of Biomedical Sciences, Chieti-Pescara University, Chieti, Italy.
authors.forename: Stella
authors.initials: S
authors.lastname: Santarone
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
authors.forename: Marta
authors.initials: M
authors.lastname: Di Nicola
authors.forename: Teresa
authors.initials: T
authors.lastname: Field
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
authors.forename: Ernesto
authors.initials: E
authors.lastname: Ayala
authors.forename: William
authors.initials: W
authors.lastname: Janssen
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Kharfan-Dabaja
authors.forename: Leonel
authors.initials: L
authors.lastname: Ochoa
authors.forename: Lia
authors.initials: L
authors.lastname: Perez
authors.forename: Janelle
authors.initials: J
authors.lastname: Perkins
authors.forename: Jyoti
authors.initials: J
authors.lastname: Raychaudhuri
authors.forename: Hugo
authors.initials: H
authors.lastname: Fernandez
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002066:Busulfan / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality* / Q000628:therapy*; D012189:Retrospective Studies; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D007166:Immunosuppressive Agents; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D016559:Tacrolimus; D008727:Methotrexate